Search results for "SYNERGISM"
showing 10 items of 153 documents
Increased toxicity of cocaine on human hepatocytes induced by ethanol: role of GSH.
1999
Increased toxicity of cocaine to human hepatocytes is observed when cells are simultaneously incubated with ethanol. Ethanol might exacerbate cocaine hepatocyte toxicity by three different pathways: a) by increasing the oxidative metabolism of cocaine and hence the oxidative damage; b) by the formation of a more toxic metabolite, namely cocaethylene; or c) by decreasing the defence mechanisms of the cell (i.e. GSH). In the present study, experiments were conducted to investigate the feasibility of these hypotheses. In hepatocytes preincubated for 48 hr with ethanol, neither significant changes in cocaine metabolism nor cytotoxicity were found despite differences in hepatocyte p-nitrophenol …
Small volume resuscitation with tempol is detrimental during uncontrolled hemorrhagic shock in rats.
2005
In a previous study, titration of a hypertonic saline (HTS) solution during severe uncontrolled hemorrhagic shock (UHS) failed to reduce mortality. In a separate study, a novel antioxidant, polynitroxylated albumin (PNA) plus tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl), infused during shock increased long-term survival. We hypothesized that combining potent antioxidants with a hypertonic solution during UHS would preserve the logistical advantage of small volume resuscitation and improve survival.An UHS outcome model in rats was used. UHS phase I (90 min) included blood withdrawal of 30 ml/kg over 15 min, followed by tail amputation for uncontrolled bleeding. At 20 min, rats wer…
Morphine potentiates the impairing effects of neuroleptics on two-way active conditioned avoidance response in male mice
2004
The dopaminergic and opioid systems have effects on the conditioned avoidance response (CAR), although the possible interaction between these systems on this behaviour has not been studied. The effects of morphine (12.6 mg/kg), haloperidol (0.075 mg/kg), sulpiride (20 mg/kg) and risperidone (0.1 mg/kg) alone as well as morphine combined with these dopamine (DA) antagonists on the acquisition and performance of the CAR were explored in mice. Morphine increased avoidances but this seemed secondary to a rise in activity levels. All DA antagonists impaired CAR in the acquisition phase but only haloperidol disrupted performance. The combination of morphine plus neuroleptics impaired acquisition …
Glutathione and the rate of cellular proliferation determine tumour cell sensitivity to tumour necrosis factor in vivo.
1997
Low rates of cellular proliferation are associated with low GSH content and enhanced sensitivity of Ehrlich ascites-tumour (EAT) cells to the cytotoxic effects of recombinant human tumour necrosis factor (rhTNF-alpha). Buthionine sulphoximine, a selective inhibitor of GSH synthesis, inhibited tumour growth and increased rhTNF-alpha cytoxicity in vitro. Administration of sublethal doses (10(6)units/kg per day) of rhTNF-alpha to EAT-bearing mice promoted oxidative stress (as measured by increases in intracellular peroxide levels, O2(-); generation and mitochondrial GSSG) and resulted in a slight reduction (19%) in tumour cell number when controls showed the highest rate of cellular proliferat…
The nicardipine-isoprenaline interaction in human and guinea-pig isolated airways
1994
Summary— The effects of the dihydropyridine calcium antagonist nicardipine on the concentration-response curves of relaxant compounds acting through the adenylate-cyclase/cAMP system (isoprenaline, forskolin, adenosine and theophylline) or by the cGMP pathway (sodium nitroprusside) were studied on human isolated bronchus and guinea-pig isolated trachea. These effects were compared with those of nifedipine (a dihydropyridine derivative) and theophylline (a non-selective phosphodiesterase inhibitor). Nicardipine, in the range of 0.01 to 1 μM, significantly potentiated the relaxant effects of isoprenaline, forskolin, adenosine and theophylline, whereas the effects of sodium nitroprusside were …
Growth hormone potentiates thyroid hormone effects on post-exercise phosphocreatine recovery in skeletal muscle.
2012
International audience; OBJECTIVE: The aim of the study was to determine the respective impact of thyroxine and growth hormone on in vivo skeletal mitochondrial function assessed via post exercise phosphocreatine recovery. DESIGN: The hind leg muscles of 32 hypophysectomized rats were investigated using (31)P nuclear magnetic resonance spectroscopy at rest and during the recovery period following a non tetanic stimulation of the sciatic nerve. Each rat was supplemented with hydrocortisone and was randomly assigned to one of the 4 groups: the group Hx was maintained in hypopituitarism., the group HxT was treated with 1 μg/100g/day of thyroxine (T4), the group HxG with 0.2 IU/kg/day of recomb…
Glutamine potentiates TNF-α-induced tumor cytotoxicity
2001
L-glutamine (Gln) sensitizes tumor cells to tumor necrosis factor (TNF)-alpha-induced cytotoxicity. The type and mechanism of cell death induced by TNF-alpha was studied in Ehrlich ascites tumor (EAT)-bearing mice fed a Gln-enriched diet (GED; where 30% of the total dietary nitrogen was from Gln). A high rate of Gln oxidation promotes a selective depletion of mitochondrial glutathione (mtGSH) content to approximately 58% of the level found in tumor mitochondria of mice fed a nutritionally complete elemental diet (standard diet, SD). The mechanism of mtGSH depletion involves a glutamate-induced inhibition of GSH transport from the cytosol into mitochondria. The increase in reactive oxygen in…
Additive Effects of Salmeterol and Fluticasone or Theophylline in COPD
2000
ss(2)-Agonists and corticosteroids or theophylline can interact to produce beneficial effects on airway function in asthma, but this has not been established in COPD.Eighty patients with well-controlled COPD were randomized to receive 3 months of treatment in one of four treatment groups: (1) salmeterol, 50 microg bid; (2) salmeterol, 50 microg, plus fluticasone propionate, 250 microg bid; (3) salmeterol, 50 microg, plus fluticasone propionate, 500 microg bid; and (4) salmeterol, 50 microg, plus titrated theophylline bid. At each visit, a dose-response curve to inhaled salbutamol was constructed using a total cumulative dose of 800 microg.A gradual increase in FEV(1) was observed with each …
In vitro anti-inflammatory effects of AZD8999, a novel bifunctional muscarinic acetylcholine receptor antagonist /β2-adrenoceptor agonist (MABA) comp…
2019
Recent evidence indicates that AZD8999 (LAS190792), a novel muscarinic acetylcholine receptor antagonist and β2-adrenoceptor agonist (MABA) in development for chronic respiratory diseases, induces potent and sustained relaxant effects in human bronchi by adressing both muscarinic acetylcholine receptors and β2-adrenoceptor. However, the anti-inflammatory effects of the AZD8999 monotherapy or in combination with corticosteroids are unknown. This study investigates the anti-inflammatory effects of AZD8999 in monotherapy and combined with fluticasone propionate in neutrophils from healthy and chronic obstructive pulmonary disease (COPD) patients. Peripheral blood neutrophils from healthy and C…
Kinetic experiments on the synergistic effect of NADH on microsomal drug oxidation.
1974
Abstract1. The synergistic effect of NADH on the NADPH-dependent mixed function oxidation of p-nitroanisole and hexobarbital can be measured both photometrically and by following the substrate-induced oxygen consumption. The increase in reaction rate is about 50% and lasts as long as NADH is present in the microsomal suspension.2. The oxidation of added NADH is increased by hexobarbital, ethylmorphine and SKF 525-A. Lineweaver-Burk transformation of the NADH oxidation rates yields straight lines for xenobiotic substrates suggesting Michaelis constants similar to those obtained from metabolic experiments. NADH oxidation in the absence of NADPH is about half as rapid as in its presence.3. Som…